Targeted Therapies

The goal of chemotherapy is to kill cancer cells that grow and divide rapidly. It also affects normal cells that are fast growing too such as cells in the skin, lining of the digestive tract and hair follicle, which can cause unwanted side effects. Drugs called targeted therapies interfere with the ways cancer cells function and reduce damage to normal cells. The ways targeted therapies work include:

New blood vessel formation (angiogenesis)

Cancer cells rely on new blood vessels to supply them with oxygen and nutrients. Drugs that block angiogenesis starve cells of their blood supply, which helps to slow or stop tumor growth. These drugs also seem to make traditional chemotherapies more effective.

Stimulation from growth signals

Cancer cells may rely on signals that tell them to grow or divide uncontrollably. Drugs that block these signals may help to slow or stop tumor growth.

Most targeted therapies are either monoclonal antibodies or small-molecule drugs.

Monoclonal antibodies are proteins that attach to substances called receptors on the surface of the cell and block signals that tell the cell what to do. They can also be used alone or with other drugs to target defects in the cancer cells or make the cancer cells more receptive to the body’s immune system. Monoclonal antibodies can also carry other drugs or substances directly to the cancer.

Ramucirumab (Cyramza)was approved in December 2014 for use in combination with the chemotherapy docetaxel (Taxotere) for the treatment of people with stage IV (metastatic) non-small cell lung cancer (NSCLC) whose cancer continued to grow while or after they took a platinum-based chemotherapy (cisplatin or carboplatin). People with EGFR mutations (see below) or ALK rearrangements (see below) whose cancer continued to grow while on an FDA-approved therapy for those conditions are also eligible to receive ramucirumab.

Bevacizumab (Avastin) was approved in 2004 for the treatment of NSCLC that is not squamous cell carcinoma. It is frequently given with traditional chemotherapy. Avastin should not be used to treat squamous cell lung cancer because in clinical trials, those with squamous cell had many more life-threatening and fatal side effects from the drug. For more information, see the Avastin website.

Small-molecule drugs can get inside the cell and stop the cell from functioning normally, which usually causes it to die. Kinase inhibitors are small-molecule drugs that interfere with cell communication and growth. More are being studied but the following is a list of those approved to treat lung cancer.

Erlotinib (Tarceva) was first approved in 2004 for the treatment of advanced-stage NSCLC after the cancer has spread after initial chemotherapy (as 2nd or 3rd line treatment) and is also approved for use as a maintenance therapy in certain cases of locally advanced NSCLC. In May 2013, Tarceva was approved for initial (1st line) treatment for advanced NSCLC when the cancer has the EGFR (epidermal growth factor receptor) mutation with certain properties, as detected by an FDA-approved test. For more information, see the Tarceva website.

Afatinib (Gilotrif)was approved in July 2013 for people people with late stage (NSCLC) when the cancer has the EGFR (epidermal growth factor receptor) gene mutation with certain properties, as detected by an FDA-approved test.

Crizotinib (Xalkori) was approved in September 2011. It targets the EML4-ALK (echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase) rearrangement. The EML4-ALK rearrangement is found in 2-7% of people with NSCLC, primarily those diagnosed with adenocarcinoma and is more common in men and never smokers. For those patients with the mutation, Xalkori has shown dramatic results. For more information, see the Xalkori website.

Ceritinib (Zykadia) was approved in April 2014. It also targets the EML4-ALK rearrangement and is approved only for those previously treated with Xalkori.

Gefitinib (Iressa) was approved in the US in July 2015 for NSCLC with the EGFR mutation as confirmed by an FDA-approved test. Iressa was briefly approved in the US before the test was developed to identify who would benefit. For more information, see the Iressa website.